Azole fungicides, designed to halt fungal growth by specific inhibition of fungal cytochrome P450 (CYP51), inhibit cytochrome P450s involved in the metabolism of xenobiotics in several non-target organisms thus raising environmental concern. The present study investigates the degree by which inhibition strengths of azoles toward cytochrome P450 in rat liver, the insect Chironomus riparius larvae and the snail Lymnaea stagnalis can be extrapolated from estimated in silico affinities. Azoles’ affinities toward human cytochrome P450 isoforms involved in xenobiotic metabolism (CYP3A4, CYP2C9 and CYP2D6) as well as fungal CYP51 were estimated with a ligand-protein docking model based on the ChemScore scoring function. Estimated affinities toward the selected enzymatic structures correlated strongly with measured inhibition strengths in rat liver (ChemScore vs. logIC₅₀ among cytochrome P450 isoforms: −0.662 < r < −0.891, n = 17 azoles), while weaker correlations were found for C. riparius larvae (−0.167 < r < −0.733, n = 9) and L. stagnalis (−0.084 < r < −0.648, n = 8). Inhibition strengths toward C. riparius and rat liver activities were found to be highly correlated to each other (r: 0.857) while no significant relationship was found between either of the species and L. stagnalis. The inhibition of cytochrome P450 due to azole fungicides could be estimated in vitro and to a lesser extent in silico for C. riparius but not for L. stagnalis, possibly due to different enzymatic susceptibility toward azole inhibition among the species.

偶氮类杀菌剂旨在通过特异性抑制真菌细胞色素P450（CYP51）来停止真菌生长，抑制几种非靶标生物中涉及异源生物代谢的细胞色素P450，从而引起了环境关注。本研究调查了可以从估计的计算机模拟中推断出吡咯类化合物对大鼠肝脏，昆虫Chironomus riparius幼虫和蜗牛Lymnaea stagnalis的抑制强度的程度。亲和力。使用基于ChemScore评分功能的配体-蛋白质对接模型估算了Azoles对参与异源生物代谢的人类细胞色素P450亚型（CYP3A4，CYP2C9和CYP2D6）以及真菌CYP51的亲和力。估计的对选定酶结构的亲和力与大鼠肝脏中测得的抑制强度密切相关（在细胞色素P450亚型中，ChemScore与logIC _50的关系：-0.662 <r <-0.891，n = 17唑），而对角膜梭菌的相关性较弱。幼虫（-0.167 <R <-0.733，N = 9）和L. stagnalis（-0.084 <R <-0.648，N = 8）。对河滨梭菌的抑制强度发现大鼠和大鼠的肝活动之间存在高度相关性（r：0.857），而两个物种与stagnalis之间均无显着相关性。可以在体外估计对唑类杀真菌剂造成的细胞色素P450的抑制作用，而对于河豚草（C. riparius）而不是对胸骨乳杆菌（L. stagnalis），可以在计算机上估计其抑制程度，其程度较小，这可能是由于不同物种对唑抑制作用的酶敏感性不同。